Immune-checkpoint inhibitors (ICIs) are monoclonal antibodies to cytotoxic T lymphocyte antigen-4 (CTLA-4), programmed cell death-1 (PD-1), and its ligand (PD-L1). ICIs are promising agent for treatment of malignant diseases.
However, ICIs may induce immune-related adverse events (irAEs) in several organs, including skin, gastrointestinal tracts, liver, lung, nervous systems, and endocrine organs.
The Endocrine irAEs include hypopituitarism, primary adrenal insufficiency, thyroid dysfunction, hypoparathyroidism, and type 1 diabetes.
The incidence of thyroid irAEs following treatment with anti-PD-1 antibodies is 5-10%, and higher than that observed with anti-CTLA-4 antibodies. Thyroid irAEs classified to thyrotoxicosis (suppressed levels of serum TSH, and elevated levels of serum FT4) and hypothyroidism (increased levels of serum TSH, and low levels of serum FT4). Low T3 syndrome, often seen in patients with advanced malignancies, should be considered separately.
Thyrotoxicosis develops 2-6 weeks after the administration of ICIs in most cases, and is often followed by hypothyroidism. The activation of thyroid autoimmunity seems to be associated with development of thyroid irAEs, and positivity of thyroid autoantibodies (TgAb and/or TPOAb) prior to ICIs therapy may predict thyroid irAEs.
As symptoms such as fatigue can also be observed in patients with malignancies, precise diagnosis of thyroid irAEs are therefore based on clinical manifestation, laboratory testing, ultrasound examination, and thyroid scintigrams. Thyrotoxicosis may be relieved with beta-blockers, and hypothyroidism may be treated with L-T4. The use of ICIs in patients with thyroid irAEs should be withheld until they became stable.
Positive correlation of thyroid irAEs and clinical antitumor effectiveness has been reported, and thus awareness of thyroid irAEs are necessary for clinicians.
In this symposium, we introduce the mechanism, prompt managements, and future prospects of thyroid irAEs during ICIs therapy.